Estimating risk of endometrial malignancy and other intracavitary uterine pathology in women without abnormal uterine bleeding using IETA-1 multinomial regression model: validation study.

OBJECTIVES: To assess the ability of the International Endometrial Tumor Analysis (IETA)-1 polynomial regression model to estimate the risk of endometrial cancer (EC) and other intracavitary uterine pathology in women without abnormal uterine bleeding. METHODS: This was a retrospective study, in which we validated the IETA-1 model on the IETA-3 study cohort (n = 1745). The IETA-3 study is a prospective observational multicenter study. It includes women without vaginal bleeding who underwent a standardized transvaginal ultrasound examination in one of seven ultrasound centers between January 2011 and December 2018. The ultrasonography was performed either as part of a routine gynecological examination, during follow-up of non-endometrial pathology, in the work-up before fertility treatment or before treatment for uterine prolapse or ovarian pathology. Ultrasonographic findings were described using IETA terminology and were compared with histology, or with results of clinical and ultrasound follow-up of at least 1 year if endometrial sampling was not performed. The IETA-1 model, which was created using data from patients with abnormal uterine bleeding, predicts four histological outcomes: (1) EC or endometrial intraepithelial neoplasia (EIN); (2) endometrial polyp or intracavitary myoma; (3) proliferative or secretory endometrium, endometritis, or endometrial hyperplasia without atypia; and (4) endometrial atrophy. The predictors in the model are age, body mass index and seven ultrasound variables (visibility of the endometrium, endometrial thickness, color score, cysts in the endometrium, non-uniform echogenicity of the endometrium, presence of a bright edge, presence of a single dominant vessel). We analyzed the discriminative ability of the model (area under the receiver-operating-characteristics curve (AUC); polytomous discrimination index (PDI)) and evaluated calibration of its risk estimates (observed/expected ratio). RESULTS: The median age of the women in the IETA-3 cohort was 51 (range, 20-85) years and 51% (887/1745) of the women were postmenopausal. Histology showed EC or EIN in 29 (2%) women, endometrial polyps or intracavitary myomas in 1094 (63%), proliferative or secretory endometrium, endometritis, or hyperplasia without atypia in 144 (8%) and endometrial atrophy in 265 (15%) women. The endometrial sample had insufficient material in five (0.3%) cases. In 208 (12%) women who did not undergo endometrial sampling but were followed up for at least 1 year without clinical or ultrasound signs of endometrial malignancy, the outcome was classified as benign. The IETA-1 model had an AUC of 0.81 (95% CI, 0.73-0.89, n = 1745) for discrimination between malignant (EC or EIN) and benign endometrium, and the observed/expected ratio for EC or EIN was 0.51 (95% CI, 0.32-0.82). The model was able to categorize the four histological outcomes with considerable accuracy: the PDI of the model was 0.68 (95% CI, 0.62-0.73) (n = 1532). The IETA-1 model discriminated very well between endometrial atrophy and all other intracavitary uterine conditions, with an AUC of 0.96 (95% CI, 0.95-0.98). Including only patients in whom the endometrium was measurable (n = 1689), the model's AUC was 0.83 (95% CI, 0.75-0.91), compared with 0.62 (95% CI, 0.52-0.73) when using endometrial thickness alone to predict malignancy (difference in AUC, 0.21; 95% CI, 0.08-0.32). In postmenopausal women with measurable endometrial thickness (n = 848), the IETA-1 model gave an AUC of 0.81 (95% CI, 0.71-0.91), while endometrial thickness alone gave an AUC of 0.70 (95% CI, 0.60-0.81) (difference in AUC, 0.11; 95% CI, 0.01-0.20). CONCLUSION: The IETA-1 model discriminates well between benign and malignant conditions in the uterine cavity in patients without abnormal bleeding, but it overestimates the risk of malignancy. It also discriminates well between the four histological outcome categories. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Addendum to the consensus opinion from the International Deep Endometriosis Analysis (IDEA) group: sonographic evaluation of the parametrium.

Preoperative sonographic staging in patients with suspected parametrial endometriosis is essential to plan the surgical intervention and to anticipate the need for a multidisciplinary approach, and hence optimize surgical outcome. The results of a recent metanalysis suggest that defining more accurately the ultrasonographic criteria of parametrial involvement in endometriosis is needed. The aim of this addendum to the IDEA-consensus is to highlight the sonographic characteristics of the parametrium and identify ultrasound techniques to diagnose deep endometriosis in this area. This article is protected by copyright. All rights reserved.

Diagnostic accuracy of ultrasound signs for detecting adnexal torsion: systematic review and meta-analysis.

OBJECTIVE: To evaluate the diagnostic accuracy of different ultrasound signs for diagnosing adnexal torsion, using surgery as the reference standard. METHODS: This was a systematic review and meta-analysis of studies published between January 1990 and November 2021 evaluating ovarian edema, adnexal mass, ovarian Doppler flow findings, the whirlpool sign and pelvic fluid as ultrasound signs (index tests) for detecting adnexal torsion, using surgical findings as the reference standard. The search for studies was performed in PubMed/MEDLINE, CINAHL, Scopus, The Cochrane Library, ClinicalTrials.gov and Web of Science databases. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to evaluate the quality of the studies. Pooled sensitivity, specificity, and positive and negative likelihood ratios were calculated separately, and the post-test probability of adnexal torsion following a positive or negative test was also determined. RESULTS: The search identified 1267 citations after excluding duplicates. Eighteen studies were ultimately included in the qualitative and quantitative syntheses. Eight studies (809 patients) analyzed the presence of ovarian edema, eight studies (1044 patients) analyzed the presence of an adnexal mass, 14 studies (1742 patients) analyzed ovarian Doppler flow, six studies (545 patients) analyzed the whirlpool sign and seven studies (981 patients) analyzed the presence of pelvic fluid as ultrasound signs of adnexal torsion. Overall, the quality of most studies was considered to be moderate or good. However, there was a high risk of bias in the patient-selection and index-text domains (with the exception of the whirlpool sign) in a significant proportion of studies. Pooled sensitivity, specificity, and positive and negative likelihood ratios of each ultrasound sign were 58%, 86%, 4.0 and 0.49 for ovarian edema, 69%, 46%, 1.3 and 0.67 for adnexal mass, 65%, 91%, 7.6 and 0.38 for the whirlpool sign, 53%, 95%, 11.0 and 0.49 for ovarian Doppler findings and 55%, 69%, 1.7 and 0.66 for pelvic fluid. Heterogeneity was high for all analyses. CONCLUSIONS: The presence of an adnexal mass or pelvic fluid have poor diagnostic accuracy as ultrasound signs of adnexal torsion, while the presence of ovarian edema, the whirlpool sign and decreased or absent ovarian Doppler flow have good specificity but moderate sensitivity for detecting adnexal torsion. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Benign descriptors and ADNEX in two-step strategy to estimate risk of malignancy in ovarian tumors: retrospective validation in IOTA5 multicenter cohort.

OBJECTIVE: Previous work has suggested that the ultrasound-based benign simple descriptors (BDs) can reliably exclude malignancy in a large proportion of women presenting with an adnexal mass. This study aimed to validate a modified version of the BDs and to validate a two-step strategy to estimate the risk of malignancy, in which the modified BDs are followed by the Assessment of Different NEoplasias in the adneXa (ADNEX) model if modified BDs do not apply. METHODS: This was a retrospective analysis using data from the 2-year interim analysis of the International Ovarian Tumor Analysis (IOTA) Phase-5 study, in which consecutive patients with at least one adnexal mass were recruited irrespective of subsequent management (conservative or surgery). The main outcome was classification of tumors as benign or malignant, based on histology or on clinical and ultrasound information during 1 year of follow-up. Multiple imputation was used when outcome based on follow-up was uncertain according to predefined criteria. RESULTS: A total of 8519 patients were recruited at 36 centers between 2012 and 2015. We excluded patients who were already in follow-up at recruitment and all patients from 19 centers that did not fulfil our criteria for good-quality surgical and follow-up data, leaving 4905 patients across 17 centers for statistical analysis. Overall, 3441 (70%) tumors were benign, 978 (20%) malignant and 486 (10%) uncertain. The modified BDs were applicable in 1798/4905 (37%) tumors, of which 1786 (99.3%) were benign. The two-step strategy based on ADNEX without CA125 had an area under the receiver-operating-characteristics curve (AUC) of 0.94 (95% CI, 0.92-0.96). The risk of malignancy was slightly underestimated, but calibration varied between centers. A sensitivity analysis in which we expanded the definition of uncertain outcome resulted in 1419 (29%) tumors with uncertain outcome and an AUC of the two-step strategy without CA125 of 0.93 (95% CI, 0.91-0.95). CONCLUSION: A large proportion of adnexal masses can be classified as benign by the modified BDs. For the remaining masses, the ADNEX model can be used to estimate the risk of malignancy. This two-step strategy is convenient for clinical use. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Diagnostic accuracy of transvaginal ultrasound for detection of endometriosis using International Deep Endometriosis Analysis (IDEA) approach: prospective international pilot study.

OBJECTIVE: To evaluate the diagnostic accuracy of transvaginal ultrasound (TVS) in predicting deep endometriosis (DE) following the International Deep Endometriosis Analysis (IDEA) consensus methodology. METHODS: This was an international multicenter prospective diagnostic accuracy study involving eight centers across six countries (August 2018-November 2019). Consecutive participants with endometriosis suspected based on clinical symptoms or historical diagnosis of endometriosis were included. The index test was TVS performed preoperatively in accordance with the IDEA consensus statement. At each center, the index test was interpreted by a single sonologist. Reference standards were: (1) direct visualization of endometriosis at laparoscopy, as determined by a non-blinded surgeon with expertise in endometriosis surgery; and (2) histological assessment of biopsied/excised tissue. Surgery was performed within 12 months following the index TVS. Accuracy, sensitivity, specificity, positive and negative predictive values (PPV and NPV) and positive and negative likelihood ratios (LR+ and LR-) of TVS in the diagnosis of DE were calculated. RESULTS: Included in the study were 273 participants with complete clinical, TVS, laparoscopic and histological data. Of these, based on histology, 256 (93.8%) were confirmed to have endometriosis, including superficial endometriosis, and 190 (69.6%) were confirmed to have DE. Based on surgical visualization, 207/273 (75.8%) patients had DE. For DE overall, the diagnostic performance of TVS based on surgical visualization as the reference standard was as follows: accuracy, 86.1%; sensitivity, 88.4%; specificity, 78.8%; PPV, 92.9%; NPV, 68.4%; LR+, 4.17; LR-, 0.15, and the diagnostic performance of TVS based on histology as the reference standard was as follows: accuracy, 85.9%; sensitivity, 89.8%; specificity, 75.9%; PPV, 90.4%; NPV, 74.6%; LR+, 3.72; LR-, 0.13. CONCLUSIONS: Using the IDEA consensus methodology provides strong diagnostic accuracy for TVS assessment of DE. We found a higher TVS detection rate of DE overall than that reported by the most recent meta-analysis on the topic (sensitivity, 79%), albeit with a lower specificity. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Ultrasound features of endometrial pathology in women without abnormal uterine bleeding: results from the International Endometrial Tumor Analysis study (IETA3).

OBJECTIVES: The primary aim of this study was to describe the ultrasound features of various endometrial and other intracavitary pathologies in women without abnormal uterine bleeding (AUB) using the International Endometrial Tumor Analysis (IETA) terminology. The secondary aim was to compare our findings with published data on women with AUB. METHODS: This was a prospective observational study of women presenting at one of seven centers specialized in gynecological ultrasonography, from 2011 until 2018, for indications unrelated to AUB. All patients underwent transvaginal ultrasound using the IETA examination and measurement techniques. Ultrasonography was performed as part of routine gynecological examination or follow-up of non-endometrial pathology, or as part of the work-up before undergoing treatment for infertility, uterine prolapse or ovarian pathology. Ultrasound findings were described using the IETA terminology. Endometrial sampling was performed after the ultrasound scan. The histological endpoints were endometrial atrophy, proliferative or secretory endometrium, endometrial hyperplasia without atypia, endometrial polyp, intracavitary leiomyoma, endometrial intraepithelial neoplasia (EIN), endometrial cancer (EC) and insufficient tissue. The findings in our cohort of women without AUB were compared with those in a published cohort of women with AUB who were examined with transvaginal ultrasound between 2012 and 2015 using the same IETA examination technique and terminology. RESULTS: In this study (IETA3), we included 1745 women without AUB who underwent a standardized transvaginal ultrasound examination followed by either endometrial sampling with histological diagnosis (n = 1537) or at least 1 year of clinical and ultrasound follow-up (n = 208). Of these, 858 (49.2%) women were premenopausal and 887 (50.8%) were postmenopausal. Histology showed the presence of EC and/or EIN in 29 (1.7%) women, endometrial polyps in 1028 (58.9%), intracavitary myomas in 66 (3.8%), proliferative or secretory changes or hyperplasia without atypia in 144 (8.3%), endometrial atrophy in 265 (15.2%) and insufficient tissue in five (0.3%). Most cases of EC or EIN (25/29 (86.2%)) were diagnosed after menopause. The mean endometrial thickness in women with EC or EIN was 11.2 mm (95% CI, 8.9-13.6 mm), being on average 2.4 mm (95% CI, 0.3-4.6 mm) thicker than their benign counterparts. Women with malignant endometrial pathology manifested more frequently non-uniform echogenicity (22/29 (75.9%)) than did those with benign endometrial pathology (929/1716 (54.1%)) (difference, +21.8% (95% CI, +4.2% to +39.2%)). Moderate to abundant vascularization (color score 3-4) was seen in 31.0% (9/29) of cases with EC or EIN compared with 12.8% (220/1716) of those with a benign outcome (difference, +18.2% (95% CI, -0.5% to +36.9%)). Multiple multifocal vessels were recorded in 24.1% (7/29) women with EC or EIN vs 4.0% (68/1716) of those with a benign outcome (difference, +20.2% (95% CI, +4.6% to +35.7%)). A regular endometrial-myometrial junction was seen less frequently in women with EC or EIN (19/29 (65.5%)) vs those with a benign outcome (1412/1716 (82.3%)) (difference, -16.8% (95% CI, -34.2% to +0.6%)). In women with endometrial polyps without AUB, a single dominant vessel was the most frequent vascular pattern (666/1028 (64.8%)). In women with EC, both in those with and those without AUB, the endometrium usually manifested heterogeneous echogenicity, but the endometrium was on average 8.6 mm (95% CI, 5.2-12.0 mm) thinner and less intensely vascularized (color score 3-4: difference, -26.8% (95% CI, -52.2% to -1.3%)) in women without compared to those with AUB. In both pre- and postmenopausal women, asymptomatic endometrial polyps were associated with a thinner endometrium, and they manifested more frequently a bright edge, a regular endometrial-myometrial junction and a single dominant vessel than did polyps in symptomatic women, and they were less intensely vascularized. CONCLUSIONS: We describe the typical ultrasound features of EC, polyps and other intracavitary histologies using IETA terminology in women without AUB. Our findings suggest that the presence of asymptomatic polyps or endometrial malignancy may be accompanied by thinner and less intensely vascularized endometria than their symptomatic counterparts. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Strengths and limitations of diagnostic tools for endometriosis and relevance in diagnostic test accuracy research.

Endometriosis is a chronic systemic disease that can cause pain, infertility and reduced quality of life. Diagnosing endometriosis remains challenging, which yields diagnostic delays for patients. Research on diagnostic test accuracy in endometriosis can be difficult due to verification bias, as not all patients with endometriosis undergo definitive diagnostic testing. The purpose of this State-of-the-Art Review is to provide a comprehensive update on the strengths and limitations of the diagnostic modalities used in endometriosis and discuss the relevance of diagnostic test accuracy research pertaining to each. We performed a comprehensive literature review of the following methods: clinical assessment including history and physical examination, biomarkers, diagnostic imaging, surgical diagnosis and histopathology. Our review suggests that, although non-invasive diagnostic methods, such as clinical assessment, ultrasound and magnetic resonance imaging, do not yet qualify formally as replacement tests for surgery in diagnosing all subtypes of endometriosis, they are likely to be appropriate for advanced stages of endometriosis. We also demonstrate in our review that all methods have strengths and limitations, leading to our conclusion that there should not be a single gold-standard diagnostic method for endometriosis, but rather, multiple accepted diagnostic methods appropriate for different circumstances. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Diagnostic accuracy of sliding sign for detecting pouch of Douglas obliteration and bowel involvement in women with suspected endometriosis: systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review and meta-analysis was to evaluate the diagnostic accuracy of the sliding sign on transvaginal ultrasound (TVS) in detecting pouch of Douglas obliteration and bowel involvement in patients with suspected endometriosis, using laparoscopy as the reference standard. METHODS: A search for studies evaluating the role of the sliding sign in the assessment of pouch of Douglas obliteration and/or bowel involvement using laparoscopy as the reference standard published from January 2000 to October 2021 was performed in PubMed/MEDLINE, Web of Science, CINAHL, The Cochrane Library, ClinicalTrials.gov and SCOPUS databases. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to evaluate the quality of the studies. Analyses were performed using MIDAS and METANDI commands in STATA. RESULTS: A total of 334 citations were identified. Eight studies were included in the analysis, resulting in 938 and 963 patients available for analysis of the diagnostic accuracy of the sliding sign for pouch of Douglas obliteration and bowel involvement, respectively. The mean prevalence of pouch of Douglas obliteration was 37% and the mean prevalence of bowel involvement was 23%. The pooled estimated sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of the sliding sign on TVS for detecting pouch of Douglas obliteration were 88% (95% CI, 81-93%), 94% (95% CI, 91-96%), 15.3 (95% CI, 10.2-22.9), 0.12 (95% CI, 0.07-0.21) and 123 (95% CI, 62-244), respectively. The heterogeneity was moderate for sensitivity and low for specificity for detecting pouch of Douglas obliteration. The pooled estimated sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of the sliding sign on TVS for detecting bowel involvement were 81% (95% CI, 64-91%), 95% (95% CI, 91-97%), 16.0 (95% CI, 9.0-28.6), 0.20 (95% CI, 0.10-0.40) and 81 (95% CI, 34-191), respectively. The heterogeneity for the meta-analysis of diagnostic accuracy for bowel involvement was high. CONCLUSION: The sliding sign on TVS has good diagnostic performance for predicting pouch of Douglas obliteration and bowel involvement in women with suspected endometriosis. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Diagnostic accuracy of transvaginal sonography for detecting parametrial involvement in women with deep endometriosis: systematic review and meta-analysis.

OBJECTIVE: To evaluate the accuracy of transvaginal sonography (TVS) for detecting parametrial deep endometriosis, using laparoscopy as the reference standard. METHODS: A search was performed in PubMed/MEDLINE and Web of Science for studies evaluating TVS for detecting parametrial involvement in women with suspected deep endometriosis, as compared with laparoscopy, from January 2000 to December 2020. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to evaluate the quality of the studies. Pooled sensitivity, specificity and positive and negative likelihood ratios for TVS in the detection of parametrial deep endometriosis were calculated, and the post-test probability of parametrial deep endometriosis following a positive or negative test was determined. RESULTS: The search identified 134 citations. Four studies, comprising 560 patients, were included in the analysis. The mean prevalence of parametrial deep endometriosis at surgery was 18%. Overall, the pooled estimated sensitivity, specificity and positive and negative likelihood ratios of TVS in the detection of parametrial deep endometriosis were 31% (95% CI, 10-64%), 98% (95% CI, 95-99%), 18.5 (95% CI, 8.8-38.9) and 0.70 (95% CI, 0.46-1.06), respectively. The diagnostic odds ratio was 26 (95% CI, 10-68). Heterogeneity was high. Visualization of a lesion suspected to be parametrial deep endometriosis on TVS increased significantly the post-test probability of parametrial deep endometriosis. CONCLUSION: TVS has high specificity but low sensitivity for the detection of parametrial deep endometriosis. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Vessel morphology depicted by three-dimensional power Doppler ultrasound as second-stage test in adnexal tumors that are difficult to classify: prospective diagnostic accuracy study.

OBJECTIVES: To assess whether vessel morphology depicted by three-dimensional (3D) power Doppler ultrasound improves discrimination between benignity and malignancy if used as a second-stage test in adnexal masses that are difficult to classify. METHODS: This was a prospective observational international multicenter diagnostic accuracy study. Consecutive patients with an adnexal mass underwent standardized transvaginal two-dimensional (2D) grayscale and color or power Doppler and 3D power Doppler ultrasound examination by an experienced examiner, and those with a 'difficult' tumor were included in the current analysis. A difficult tumor was defined as one in which the International Ovarian Tumor Analysis (IOTA) logistic regression model-1 (LR-1) yielded an ambiguous result (risk of malignancy, 8.3% to 25.5%), or as one in which the ultrasound examiner was uncertain regarding classification as benign or malignant when using subjective assessment. Even when the ultrasound examiner was uncertain, he/she was obliged to classify the tumor as most probably benign or most probably malignant. For each difficult tumor, one researcher created a 360° rotating 3D power Doppler image of the vessel tree in the whole tumor and another of the vessel tree in a 5-cm3 spherical volume selected from the most vascularized part of the tumor. Two other researchers, blinded to the patient's history, 2D ultrasound findings and histological diagnosis, independently described the vessel tree using predetermined vessel features. Their agreed classification was used. The reference standard was the histological diagnosis of the mass. The sensitivity of each test for discriminating between benign and malignant difficult tumors was plotted against 1 - specificity on a receiver-operating-characteristics diagram, and the test with the point furthest from the reference line was considered to have the best diagnostic ability. RESULTS: Of 2403 women with an adnexal mass, 376 (16%) had a difficult mass. Ultrasound volumes were available for 138 of these cases. In 79/138 masses, the ultrasound examiner was uncertain about the diagnosis based on subjective assessment, in 87/138, IOTA LR-1 yielded an ambiguous result and, in 28/138, both methods gave an uncertain result. Of the masses, 38/138 (28%) were malignant. Among tumors that were difficult to classify as benign or malignant by subjective assessment, the vessel feature 'densely packed vessels' had the best discriminative ability (sensitivity 67% (18/27), specificity 83% (43/52)) and was slightly superior to subjective assessment (sensitivity 74% (20/27), specificity 60% (31/52)). In tumors in which IOTA LR-1 yielded an ambiguous result, subjective assessment (sensitivity 82% (14/17), specificity 79% (55/70)) was superior to the best vascular feature, i.e. changes in the diameter of vessels in the whole tumor volume (sensitivity 71% (12/17), specificity 69% (48/70)). CONCLUSION: Vessel morphology depicted by 3D power Doppler ultrasound may slightly improve discrimination between benign and malignant adnexal tumors that are difficult to classify by subjective ultrasound assessment. For tumors in which the IOTA LR-1 model yields an ambiguous result, subjective assessment is superior to vessel morphology as a second-stage test. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Two-dimensional transvaginal sonography vs saline contrast sonohysterography for diagnosing endometrial polyps: systematic review and meta-analysis.

OBJECTIVE: To compare the diagnostic performance of two-dimensional transvaginal sonography (TVS) and saline contrast sonohysterography (SCSH) for the diagnosis of endometrial polyps in studies that used both tests in the same group of patients. METHODS: This was a systematic review and meta-analysis. An extensive search was conducted of Medline (PubMed), Cochrane Library and Web of Science, for studies comparing the diagnostic performance of TVS and SCSH for identifying endometrial polyps, published between January 1990 and December 2019, that reported a definition of endometrial polyp on TVS and SCSH and used pathologic analysis as the reference standard. Quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. A random-effects model was used to determine pooled sensitivity, specificity and positive and negative likelihood ratios of TVS and SCSH in the detection of endometrial polyps. Subanalysis according to menopausal status was performed. RESULTS: In total, 1278 citations were identified; after exclusions, 25 studies were included in the meta-analysis. In the included studies, the risk of bias evaluated using QUADAS-2 was low for most of the four domains, except for flow and timing, which had an unclear risk of bias in 13 studies. Pooled sensitivity, specificity and positive and negative likelihood ratios for TVS in the detection of endometrial polyps were 55.0% (95% CI, 46.0-64.0%), 91.0% (95% CI, 86.0-94.0%), 5.8 (95% CI, 3.9-8.7) and 0.5 (95% CI, 0.41-0.61), respectively. The corresponding values for SCSH were 92.0% (95% CI, 87.0-95.0%), 93.0% (95% CI, 91.0-95.0%), 13.9 (95% CI, 9.9-19.5) and 0.08 (95% CI, 0.05-0.14), respectively. Significant differences were found when comparing the methods in terms of sensitivity (P < 0.001), but not for specificity (P = 0.0918). Heterogeneity was high for TVS and moderate for SCSH. On subanalysis according to menopausal status, SCSH was found to have higher diagnostic accuracy in both pre- and postmenopausal women; sensitivity and specificity did not differ significantly between the groups for either TVS or SCSH. CONCLUSION: Given that SCSH has better diagnostic positive and negative likelihood ratios than does TVS in both pre- and postmenopausal women, those with clinical suspicion of endometrial polyps should undergo SCSH if TVS findings are inconclusive. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Ecografía transvaginal bidimensional vs histerosonografía con contraste salino para el diagnóstico de pólipos endometriales: revisión sistemática y metaanálisis OBJETIVO: Comparar el desempeño del diagnóstico de la ecografía transvaginal bidimensional (TVS, por sus siglas en inglés) y la histerosonografía con contraste salino (SCSH, por sus siglas en inglés) para el diagnóstico de pólipos endometriales en estudios que utilizaron ambas pruebas en el mismo grupo de pacientes. MÉTODOS: Este estudio fue una revisión sistemática y metaanálisis. El estudio realizó una extensa búsqueda en Medline (PubMed), Cochrane Library y Web of Science de estudios en los que se había comparado el desempeño del diagnóstico de la TVS y la SCSH para identificar pólipos endometriales, publicados entre enero de 1990 y diciembre de 2019, que incluyeran una definición de pólipo endometrial en la TVS y la SCSH y utilizaran el análisis patológico como estándar de referencia. La calidad de los estudios incluidos se evaluó mediante la herramienta de Evaluación de Calidad de los Estudios de Precisión en el Diagnóstico-2 (QUADAS-2, por sus siglas en inglés). Se utilizó un modelo de efectos aleatorios para determinar la sensibilidad combinada, la especificidad, los cocientes de verosimilitud positivos y negativos de la TVS y la SCSH en la detección de pólipos endometriales. Se realizó un subanálisis en función del estatus de la menopausia. RESULTADOS: Se identificaron un total de 1278 citas, de las cuales se incluyeron 25 estudios en el metaanálisis. En los estudios incluidos, el riesgo de sesgo evaluado mediante QUADAS-2 fue bajo para la mayoría de los cuatro dominios, excepto para el flujo y el tiempo, que tuvieron un riesgo de sesgo poco claro en 13 estudios. La sensibilidad combinada, la especificidad y los cocientes de verosimilitud positivos y negativos para la TVS en la detección de pólipos endometriales fueron del 55,0% (IC 95%, 46,0-64,0%), 91,0% (IC 95%, 86,0-94,0%), 5,8 (IC 95%, 3,9-8,7) y 0,5 (IC 95%, 0,41-0,61), respectivamente. Los valores correspondientes para la SCSH fueron 92,0% (IC 95%, 87,0-95,0%), 93,0% (IC 95%, 91,0-95,0%), 13,9 (IC 95%, 9,9-19,5) y 0,08 (IC 95%, 0,05-0,14), respectivamente. Se encontraron diferencias significativas al comparar los métodos respecto a la sensibilidad (P<0,001), pero no respecto a la especificidad (P=0,0918). La heterogeneidad fue alta para la TVS y moderada para la SCSH. En el subanálisis según el estado menopáusico, se determinó que la SCSH tenía una mayor precisión en el diagnóstico en las mujeres pre- y posmenopáusicas, mientras que la sensibilidad y la especificidad no difirieron significativamente entre ambos grupos, tanto para la TVS como para la SCSH. CONCLUSIÓN: Dado que la SCSH tiene mejores coeficientes de verosimilitud positivos y negativos de diagnóstico que la TVS en las mujeres pre- y posmenopáusicas, las mujeres con sospecha clínica de pólipos endometriales deberían someterse a una SCSH si los hallazgos de la TVS no son concluyentes.

Imaging in gynecological disease (17): ultrasound features of malignant ovarian yolk sac tumors (endodermal sinus tumors).

OBJECTIVE: To describe the clinical and sonographic characteristics of malignant ovarian yolk sac tumors (YSTs). METHODS: In this retrospective multicenter study, we included 21 patients with a histological diagnosis of ovarian YST and available transvaginal ultrasound images and/or videoclips and/or a detailed ultrasound report. Ten patients identified from the International Ovarian Tumor Analysis (IOTA) studies had undergone a standardized preoperative ultrasound examination, by an experienced ultrasound examiner, between 1999 and 2016. A further 11 patients were identified through medical files, for whom ultrasound images were retrieved from local image workstations and picture archiving and communication systems. All tumors were described using IOTA terminology. The collected ultrasound images and videoclips were used by two observers for additional characterization of the tumors. RESULTS: All cases were pure YSTs, except for one that was a mixed tumor (80% YST and 20% embryonal carcinoma). Median age at diagnosis was 25 (interquartile range (IQR), 19.5-30.5) years. Seventy-six percent (16/21) of women had an International Federation of Gynecology and Obstetrics (FIGO) Stage I-II tumor at diagnosis. Fifty-eight percent (11/19) of women felt pain during the ultrasound examination and one presented with ovarian torsion. Median serum α-fetoprotein (S-AFP) level was 4755 (IQR, 1071-25 303) µg/L and median serum CA 125 level was 126 (IQR, 35-227) kU/L. On ultrasound assessment, 95% (20/21) of tumors were unilateral. The median maximum tumor diameter was 157 (IQR, 107-181) mm and the largest solid component was 110 (IQR, 66-159) mm. Tumors were classified as either multilocular-solid (10/21; 48%) or solid (11/21; 52%). Papillary projections were found in 10% (2/21) of cases. Most (20/21; 95%) tumors were well vascularized (color score, 3-4) and none had acoustic shadowing. Malignancy was suspected in all cases, except in the patient with ovarian torsion, who presented a tumor with a color score of 1, which was classified as probably benign. Image and videoclip quality was considered as adequate in 18/21 cases. On review of the images and videoclips, we found that all tumors contained both solid components and cystic spaces, and that 89% (16/18) had irregular, still fine-textured and slightly hyperechoic solid tissue, giving them a characteristic appearance. CONCLUSION: Malignant ovarian YSTs are often detected at an early stage, in young women usually in the second or third decade of life, presenting with pain and markedly elevated S-AFP. On ultrasound, malignant ovarian YSTs are mostly unilateral, large and multilocular-solid or solid, with fine-textured slightly hyperechoic solid tissue and rich vascularization. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology..

Imaging in gynecological disease (20): clinical and ultrasound characteristics of adnexal torsion.

OBJECTIVES: To describe the clinical and ultrasound characteristics of adnexal torsion. METHODS: This was a retrospective study. From the operative records of the eight participating gynecological ultrasound centers, we identified patients with a surgically confirmed diagnosis of adnexal torsion, defined as surgical evidence of ovarian pedicle, paraovarian cyst and/or Fallopian tube twisted on its own axis, who had undergone preoperative ultrasound examination by an experienced examiner, between 2008 and 2018. Only cases with at least two available ultrasound images and/or videoclips (one grayscale and one with Doppler evaluation) were included. Clinical, ultrasound, surgical and histological information was retrieved from each patient's medical record and entered into an Excel file by the principal investigator at each center. In addition, two authors reviewed all available ultrasound images and videoclips of the twisted adnexa, with regard to the presence of four predefined ultrasound features reported to be characteristic of adnexal torsion: (1) ovarian stromal edema with or without peripherally displaced antral follicles, (2) the follicular ring sign, (3) the whirlpool sign and (4) absence of vascularization in the twisted organ. RESULTS: A total of 315 cases of adnexal torsion were identified. The median age of the patients was 30 (range, 1-88) years. Most patients were premenopausal (284/314; 90.4%) and presented with acute or subacute pelvic pain (305/315; 96.8%). The surgical approach was laparoscopic in 239/312 (76.6%) patients and conservative surgery (untwisting with or without excision of a lesion) was performed in 149/315 (47.3%) cases. According to the original ultrasound reports, the median largest diameter of the twisted organ was 83 (range, 30-349) mm. Free fluid in the pouch of Douglas was detected in 196/275 (71.3%) patients. Ovarian stromal edema with or without peripherally displaced antral follicles was reported in the original ultrasound report in 167/241 (69.3%) patients, the whirlpool sign in 178/226 (78.8%) patients, absent color Doppler signals in the twisted organ in 119/269 (44.2%) patients and the follicular ring sign in 51/134 (38.1%) patients. On retrospective review of images and videoclips, ovarian stromal edema with or without peripherally displaced antral follicles (201/254; 79.1%) and the whirlpool sign (139/153; 90.8%) were the most commonly detected features of adnexal torsion. CONCLUSION: Most patients with surgically confirmed adnexal torsion are of reproductive age and present with acute or subacute pain. Common ultrasound signs are an enlarged adnexa, the whirlpool sign, ovarian stromal edema with or without peripherally displaced antral follicles and free fluid in the pelvis. The follicular ring sign and absence of Doppler signals in the twisted organ are slightly less common signs. Recognizing ultrasound signs of adnexal torsion is important so that the correct treatment, i.e. surgery without delay, can be offered. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Congenital Uterine Malformation by Experts (CUME): diagnostic criteria for T-shaped uterus.

OBJECTIVES: To identify uterine measurements that are reliable and accurate to distinguish between T-shaped and normal/arcuate uterus, and define T-shaped uterus, using Congenital Uterine Malformation by Experts (CUME) methodology, which uses as reference standard the decision made most often by several independent experts. METHODS: This was a prospectively planned multirater reliability/agreement and diagnostic accuracy study, performed between November 2017 and December 2018, using a sample of 100 three-dimensional (3D) datasets of different uteri with lateral uterine cavity indentations, acquired from consecutive women between 2014 and 2016. Fifteen representative experts (five clinicians, five surgeons and five sonologists), blinded to each others' opinions, examined anonymized images of the coronal plane of each uterus and provided their independent opinion as to whether it was T-shaped or normal/arcuate; this formed the basis of the CUME reference standard, with the decision made most often (i.e. that chosen by eight or more of the 15 experts) for each uterus being considered the correct diagnosis for that uterus. Two other experienced observers, also blinded to the opinions of the other experts, then performed independently 15 sonographic measurements, using the original 3D datasets of each uterus. Agreement between the diagnoses made by the 15 experts was assessed using kappa and percent agreement. The interobserver reliability of measurements was assessed using the concordance correlation coefficient (CCC). The diagnostic test accuracy was assessed using the area under the receiver-operating-characteristics curve (AUC) and the best cut-off value was assessed by calculating Youden's index, according to the CUME reference standard. Sensitivity, specificity, negative and positive likelihood ratios (LR- and LR+) and post-test probability were calculated. RESULTS: According to the CUME reference standard, there were 20 T-shaped and 80 normal/arcuate uteri. Individual experts recognized between 5 and 35 (median, 19) T-shaped uteri on subjective judgment. The agreement among experts was 82% (kappa = 0.43). Three of the 15 sonographic measurements were identified as having good diagnostic test accuracy, according to the CUME reference standard: lateral indentation angle (AUC = 0.95), lateral internal indentation depth (AUC = 0.92) and T-angle (AUC = 0.87). Of these, T-angle had the best interobserver reproducibility (CCC = 0.87 vs 0.82 vs 0.62 for T-angle vs lateral indentation depth vs lateral indentation angle). The best cut-off values for these measurements were: lateral indentation angle ≤ 130° (sensitivity, 80%; specificity, 96%; LR+, 21.3; LR-, 0.21), lateral indentation depth ≥ 7 mm (sensitivity, 95%; specificity, 77.5%; LR+, 4.2; LR-, 0.06) and T-angle ≤ 40° (sensitivity, 80%; specificity, 87.5%; LR+, 6.4; LR-, 0.23). Most of the experts diagnosed the uterus as being T-shaped in 0% (0/56) of cases when none of these three criteria was met, in 10% (2/20) of cases when only one criterion was met, in 50% (5/10) of cases when two of the three criteria were met, and in 93% (13/14) of cases when all three criteria were met. CONCLUSIONS: The diagnosis of T-shaped uterus is not easy; the agreement among experts was only moderate and the judgement of individual experts was commonly insufficient for accurate diagnosis. The three sonographic measurements with cut-offs that we identified (lateral internal indentation depth ≥ 7 mm, lateral indentation angle ≤ 130° and T-angle ≤ 40°) had good diagnostic test accuracy and fair-to-moderate reliability and, when applied in combination, they provided high post-test probability for T-shaped uterus. In the absence of other anomalies, we suggest considering a uterus to be normal when none or only one criterion is met, borderline when two criteria are met, and T-shaped when all three criteria are met. These three CUME criteria for defining T-shaped uterus may aid in determination of its prevalence, clinical implications and best management and in the assessment of post-surgical morphologic outcome. The CUME definition of T-shaped uterus may help in the development of interventional randomized controlled trials and observational studies and in the diagnosis of uterine morphology in everyday practice, and could be adopted by guidelines on uterine anomalies to enrich their classification systems. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Ultrasonographic soft markers for detection of rectosigmoid deep endometriosis.

OBJECTIVES: The aim of this study was to evaluate the use of ultrasound (US) soft markers as a first-line imaging tool to raise suspicion of rectosigmoid (RS) involvement in women suspected of having deep endometriosis. METHODS: We included in this prospective observational study all patients with clinical suspicion of deep endometriosis who underwent diagnostic transvaginal US evaluation at our unit from January 2016 to February 2017. Several US soft markers were evaluated for prediction of RS involvement (presence of US signs of uterine adenomyosis, presence of an endometrioma, adhesion of the ovary to the uterus (reduced ovarian mobility), presence of 'kissing ovaries' (KO) and absence of the 'sliding sign'), using as the gold standard expert US examination for the presence of RS endometriosis. RESULTS: Included were 333 patients with clinical suspicion of deep endometriosis. Of these, 106 had an US diagnosis of RS endometriosis by an expert. The only significant variables found in the prediction model were absence of the sliding sign (odds ratio (OR), 13.95; 95% CI, 7.7-25.3), presence of KO (OR, 22.5; 95% CI, 4.1-124.0) and the interaction between these two variables (OR, 0.03; 95% CI, 0.004-0.28). Regarding their interaction, RS endometriosis was present when KO was absent and the sliding sign was present in 10% (19/190) of cases, when both KO and the sliding sign were present in 71.4% (5/7) of cases, when both KO and the sliding sign were absent in 60.8% (76/125) of cases and when KO was present and the sliding sign was absent in 54.5% (6/11) of cases. Thus, when the sliding sign was absent and/or KO was present, transvaginal US showed a specificity of 75% (95% CI, 69-80%) and a sensitivity of 82% (95% CI, 73-88%). CONCLUSIONS: US findings of absence of the sliding sign and/or presence of KO in patients with clinical suspicion of endometriosis should raise suspicion of RS involvement and indicate referral for expert US examination, with a low rate of false-negative diagnosis. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Imaging in gynecological disease (16): clinical and ultrasound characteristics of serous cystadenofibromas in adnexa.

OBJECTIVE: To describe the clinical and ultrasound characteristics of serous cystadenofibromas in the adnexa. METHODS: This was a retrospective study of patients identified in the International Ovarian Tumor Analysis (IOTA) database, who had a histological diagnosis of serous cystadenofibroma and had undergone preoperative ultrasound examination by an experienced ultrasound examiner, between 1999 and 2012. In the IOTA database, which contains data collected prospectively, the tumors were described using the terms and definitions of the IOTA group. In addition, three authors reviewed, first independently and then together, ultrasound images of serous cystadenofibromas and described them using pattern recognition. RESULTS: We identified 233 women with a histological diagnosis of serous cystadenofibroma. In the IOTA database, most cystadenofibromas (67.4%; 157/233) were described as containing solid components but 19.3% (45/233) were described as multilocular cysts and 13.3% (31/233) as unilocular cysts. Papillary projections were described in 52.4% (122/233) of the cystadenofibromas. In 79.5% (97/122) of the cysts with papillary projections, color Doppler signals were absent in the papillary projections. Most cystadenofibromas (83.7%; 195/233) manifested no or minimal color Doppler signals. On retrospective analysis of 201 ultrasound images of serous cystadenofibromas, using pattern recognition, 10 major types of ultrasound appearance were identified. The most common pattern was a unilocular solid cyst with one or more papillary projections, but no other solid components (25.9%; 52/201). The second most common pattern was a multilocular solid mass with small solid component(s), but no papillary projections (19.4%; 39/201). The third and fourth most common patterns were multi- or bilocular cyst (16.9%; 34/201) and unilocular cyst (11.9%; 24/201). Using pattern recognition, shadowing was identified in 39.8% (80/201) of the tumors, and microcystic appearance of the papillary projections was observed in 34 (38.6%) of the 88 tumors containing papillary projections. CONCLUSIONS: The ultrasound features of serous cystadenofibromas vary. The most common pattern is a unilocular solid cyst with one or more papillary projections but no other solid components, with absent color Doppler signals. Most serous cystadenofibromas were poorly vascularized on color Doppler examination and many manifested acoustic shadowing. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.